The study investigated the effects of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the dorsal raphe nucleus (DRN) on anxiety-related behaviour and neurochemical correlates in rats. Behaviour was assessed in the elevated plus maze test (X-maze). Lesion of the DRN reduced markedly 5-HT levels in projection areas by at least 60%. Destruction of the serotonergic neurons in the DRN changed neither anxiety-related behaviour on the elevated plus maze, nor aversion-induced 5-HT release in the brain. Exposure of the lesioned rats to the elevated plus maze increased extracellular 5-HT (148%) in the ventral hippocampus similar as in sham-lesioned (162%) and non-lesioned (160%) controls. The results demonstrate that lesioning of 5-HT neurons in the DRN does not abolish totally the control of anxiety-related behaviour.

The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is causally involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior ([1][1]). In peripheral tissues, 5-HT regulates vascular tone, gut motility,

The fact that various neuropharmacological substances have anxiolytic as well as amnesic effects suggests that neuronal mechanisms of anxiety and learning/memory closely interact. Hence, we hypothesized that differences in anxiety-related behavior could be accompanied with differences in cognition or habituation. Two rat strains with different levels of anxiety, more anxious Fischer 344 rats by Charles River (FC) and less anxious Wistar rats by Winkelmann (WW), were tested in the Morris water maze task and an open field test for habituation learning. Additionally, we investigated the effect of different light intensities on the performance in the Morris water maze and the elevated plus maze. The results of the water maze task indicate that differences in anxiety-related behavior do not go along with differences in this performance of learning/memory. Moreover, the test was not affected by different light intensities. In contrast, illumination did affect performance in the elevated plus maze test, wherein dim light provoked an anxiolytic effect in both rat strains. The findings that neither different baseline levels of anxiety nor fear modulating light conditions were accompanied by changes in the performance of rats in the Morris water maze led us to the suggestion that there is no connection between anxiety and learning/memory in this task. Contrarily, anxiety might be associated with habituation learning in the open field test, shown by the superior habituation of the anxious FC rats in comparison to the less anxious WW rats. In sum, these results indicate that anxiety and learning/memory seem to be independently regulated behaviors, whereas habituation might be more closely correlated with anxiety. Nevertheless, a general statement about the relation between emotionality and learning/memory mechanisms would be premature and the link between behaviors remains to be clarified.

Chemical warfare agents (CWAs) such as phosgene and nerve agents pose serious threats to our lives and public security, necessitating tools that can simultaneously screen multiple CWAs in seconds.

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.

The purpose of the present study was to investigate the behavioral consequences and the neurochemical correlates of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the median raphe nucleus (MRN) in rats. Anxiety-related behavior was assessed in the elevated plus maze test on days 5, 14, and 21 after lesioning. In general, behavior of MRN-lesioned rats was unchanged when compared with sham-lesioned or untreated controls. Neurochemically, microinjection of 5,7-DHT into the MRN resulted in 87.5% depletion of hippocampal 5-HT content. Using the in vivo microdialysis technique, the exposure of 5,7-DHT–lesioned rats to the elevated plus-maze failed to increase extracellular 5-HT release (94%) in the hippocampus, as shown in sham-lesioned (150%) or untreated controls (194%). Moreover, application of fenfluramine (10 mg/kg, IP) evoked a 10-fold increase in hippocampal extracellular 5-HT levels in sham-lesioned animals, whereas in 5,7-DHT lesioned rats 5-HT was only slightly increased. The results demonstrate, that a marked reduction of 5-HT release from the MRN is not necessarily accompanied by anxiolytic-like behavior.

The cholecystokinin-tetrapeptide (CCK-4) can induce panic attacks in humans. The present study investigates the effects of CCK-4 and the CCK-B receptor antagonist l-365.260 on ultrasound induced defense behavior in the rat that may model the unconditioned aspects of panic behavior in man. CCK-4 (50 μg/kg) increased the defense response induced by ultrasound (95 dB) an effect prevented by pretreatment with l-365.260 (10 μg/kg). Compared with other antipanic/panicogenic drugs the effects of CCK-4 and l-365.260 were relatively small. In conclusion, drugs acting at the CCK-B receptor appear to have only a minor role in the modulation of an unconditioned aversive response.

Overnutrition during critical developmental periods is suggested to be a risk factor for obesity and associated metabolic disorders in later life. Underlying mechanisms are unknown. Neuropeptides are essentially involved in the central nervous regulation of body weight. For instance, hypothalamic galanin (GAL) is a stimulator of food intake and body weight gain. To investigate long-term consequences of early postnatal overfeeding, the normal litter size of Wistar rats (n=10; controls) was reduced from day 3 to day 21 of life to only 3 pups per mother (small litters, SL; overnutrition). Throughout life, SL rats displayed hyperphagia (p<0.01), overweight (p<0.0001), hyperinsulinemia (p<0.01), impaired glucose tolerance (p<0.001), elevated triglycerides (p<0.001), and an increased systolic blood pressure (p<0.05). In adulthood, an increase of GAL-neurons in the arcuate hypothalamic nucleus (ARC) was found (p<0.001), positively correlated to body weight (p<0.001). A second experiment revealed hyperinsulinemia (p<0.001) and increased hypothalamic insulin levels (p<0.05) in SL rats during early postnatal life. Already on day 21 of life, i.e., at the end of the critical hypothalamic differentiation period, in SL rats the number of GAL-neurons was increased in the ARC (p<0.001), showing a positive correlation to body weight and insulin (p<0.05). In conclusion, neonatally acquired persisting malformation of hypothalamic galaninergic neurons, induced by early overfeeding and hyperinsulinism, might promote the development of overweight and syndrome X-like alterations during life.

In a recent study it has been shown that benzodiazepine receptor agonists attenuate novelty-induced suppression of feeding and increase the percentage of animals feeding in the open field. Food-deprived rats were placed in one corner of the open field containing food in the center. The number of rats beginning to eat in the first 5 min was recorded. In the present study this test was validated pharmacologically using known "anxiolytic" or "nonanxiolytic" drugs. The following substances (effective doses, given IP) increased the number of rats feeding within 5 min in the center of the open field: meprobamate (30.0–300 mg/kg), 8-OH-DPAT (10 and 30 μg/kg), ipsapirone (1.0 and 2.0 mg/kg), ritanserin (0.125–0.5 mg/kg), tropisetron (0.1–10.0 μg/kg), ondansetron (0.3–3.0 μg/kg), lisuride (0.28–0.55 mg/kg), morphine (0.3 and 1.0 mg/kg), propranolol (0.3 and 1.0 mg/kg), clozapine (1.0 mg/kg). Drugs without "anxiolytic" effects in other animal models or in humans, including amphetamine, apomorphine, haloperidol, sulpiride, and mCPP did not increase the incidence of food intake in this test. Ethanol and hexobarbital, in nonsedative doses, had no effect in this paradigm. Drugs and doses effective in the modified open-field test caused no increase in food intake in an independent food consumption test using food-deprived rats staying in the familiar cages. The results suggest that the modified open-field test can detect "anxiolytic" drug properties and is valid for the assessment of "anxiolytic" effects from different classes of drugs.

1. In the present study it was investigated whether drugs acting at the cholecystokinin (CCK)-A receptor given to rat pups may result in long-lasting changes in body weight or regulation of food intake controlled by CCK.2. From day 3 to day 10 of Life, male and female Wistar rat pups were treated with the CCK-A receptor antagonist L-364.718 and the CCK-A+B agonist CCK-8S.3. In adult rats, treated with L364.718 during suckling, the sensitivity to the acute hypophagic action of CCK-8S was weaker or abolished compared to adults treated with saline during suckling. In adult rats given CCK-8S during suckling acute treatment with CCK-8S reduced food intake to the same extent as in the group treated with saline postnatally.4. These data show that early postnatal treatment with the CCK-A receptor antagonist L364.718 has an impact on the hypophagic response to CCK-8S in later life.

s of the BAP/EBPS International Workshop on The Behavioural Pharmacology of Anxiety and Depression, Bath, UK, November 20-23: PDF Only

s of the BAP/EBPS International Workshop on The Behavioural Pharmacology of Anxiety and Depression, Bath, UK, November 20-23: PDF Only

The satiating effect of the selective cholecystokininA (CCKA) receptor agonist A71378 and the mixed A and B receptor agonist CCK-8S were compared in 24-h food-deprived rats. After systemic application of 1.6, 8.0, and 40 micrograms/kg A71378 or CCK-8S, respectively, food intake was measured for 24 h. During the first hour A71378 and CCK-8S decreased food intake similarly. Two and 4 h after treatment, the satiating effect of A71378 continued. In contrast, 2 h after administration of CCK-8S a slight effect was observed at the highest dose (40 micrograms/kg), which totally disappeared after 4 h. In summary, the effect of A71378 on food intake is longer lasting compared to CCK-8S.

The effects of CCK on food intake were investigated under fixed feeding conditions in comparison to a test meal taken after 16 h of food deprivation. The experiments were performed on young adult rats (8 weeks old) as well on aged rats (23 months old). Intraperitoneal CCK-8 (8 and 40 micrograms/kg) significantly reduced the size of a test meal following 16-h food deprivation. This effect was independent of the age of the rats. However, under fixed feeding conditions neither of the doses used in this study reduced food intake in the young adult rats, whereas the highest dose of 40 micrograms/kg did so in the aged rats. These results suggest that the hypophagic effect of exogenous CCK-8 depends on experimental conditions, food intake being reduced after a period of food deprivation but not under a fixed feeding regimen in adult animals. Furthermore, the data suggest that age is a factor contributing to the complex behavioral actions of CCK, because only old animals were more susceptible to an anorectic action of CCK under the fixed feeding schedule. An explanation may lie in an interaction of other known behavioral effects of CCK (e.g., anxiogenic, mnemonic action) with its effects under the different feeding schedules.